Meiosis-specific destruction of the Ume6p repressor by the Cdc20-directed APC/C
Meiosis-specific destruction of the Ume6p repressor by the Cdc20-directed APC/C
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DOI：
10.1016/j.molcel.2007.08.019
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发表时间：
2007-09-21
期刊：
影响因子：
16
通讯作者：
Strich, Randy
中科院分区：
文献类型：
--
作者：
Mallory, Michael J.;Cooper, Katrina F.;Strich, Randy
酵母减数分裂的发育需要基因转录瞬时波的协调诱导。本研究调查了 Ume6p 的调节，Ume6p 是减数分裂特异性基因“早期”类的有丝分裂抑制因子。蛋白质印迹分析显示，Ume6p 在减数分裂早期被 Cdc20p 破坏，Cdc20p 是后期促进复合物/环体 (APC/C) 泛素连接酶的激活剂。该对照看起来是直接的，因为 Cdc20p 和 Ume6p 在体内结合，并且 ApC/C-Cdc20 在体外泛素化 Ume6p。灭活 Cdc20p 或通过突变稳定 Ume6p，可以阻止减数分裂基因转录和减数分裂进展。在有丝分裂细胞分裂期间，Cdc20p 的蛋白激酶 A 磷酸化可保护 Ume6p 免遭破坏。减数分裂细胞中 Ume6p 的完全消除需要与减数分裂诱导剂 Ime1 p 结合。这些结果表明 Ume6p 降解是正常减数分裂基因诱导和减数分裂进展所必需的。这些发现证明转录机制与发育调控的泛素介导的蛋白水解之间存在直接联系。
Meiotic development in yeast requires the coordinated induction of transient waves of gene transcription. The present study investigates the regulation of Ume6p, a mitotic repressor of the "early" class of meiosis-specific genes. Western blot analysis revealed that Ume6p is destroyed early in meiosis by Cdc20p, an activator of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. This control appears direct as Cdc20p and Ume6p associate in vivo and ApC/C-Cdc20 ubiquitylates Ume6p in vitro. Inactivating Cdc20p, or stabilizing Ume6p through mutation, prevented meiotic gene transcription and meiotic progression. During mitotic cell division, Ume6p is protected from destruction by protein kinase A phosphorylation of Cdc20p. Complete elimination of Ume6p in meiotic cells requires association with the meiotic inducer Ime1 p. These results indicate that Ume6p degradation is required for normal meiotic gene induction and meiotic progression. These findings demonstrate a direct connection between the transcription machinery and ubiquitin-mediated proteolysis that is developmentally regulated.